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Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia

Published online by Cambridge University Press:  01 August 2018

A. M. Fiksinski Open the ORCID record for A. M. Fiksinski [Opens in a new window] ,
E. J. Breetvelt ,
Y. J. Lee ,
E. Boot ,
N. Butcher ,
L. Palmer ,
E. W. C. Chow ,
R. S. Kahn ,
J. A. S. Vorstman  and
A. S. Bassett
A. M. Fiksinski
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
E. J. Breetvelt
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
Y. J. Lee
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
E. Boot
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
N. Butcher
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
L. Palmer
Affiliation:
The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
E. W. C. Chow
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
R. S. Kahn
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
J. A. S. Vorstman
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Program in Genetics and Genome Biology, Research Institute, Toronto, Ontario, Canada Department of Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada
A. S. Bassett*
Affiliation:
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Mental Health, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
*
Author for correspondence: A. S. Bassett, E-mail: anne.bassett@utoronto.ca
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Abstract

Background

Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.

Methods

We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.

Results

The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.

Conclusion

The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.

Keywords

Adaptive functioninghigh-riskneurocognitionschizophrenia22q11DS
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 6 , April 2019 , pp. 1047 - 1054
Copyright
Copyright © Cambridge University Press 2018 

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References

Antshel, KM, Shprintzen, R, Fremont, W, Higgins, AM, Faraone, SV and Kates, WR (2010) Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study. Journal of the American Academy of Child and Adolescent Psychiatry 49, 333–344.Google Scholar
Bassett, AS, Caluseriu, O, Weksberg, R, Young, DA and Chow, EW (2007) Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biological Psychiatry 61, 1135–1140.Google Scholar
Bassett, AS, Chow, EW, Husted, J, Weksberg, R, Caluseriu, O, Webb, GD and Gatzoulis, MA (2005) Clinical features of 78 adults with 22q11 deletion syndrome. American Journal of Medical Genetics A 138, 307–313.Google Scholar
Bellack, AS, Green, MF, Cook, JA, Fenton, W, Harvey, PD, Heaton, RK, Laughren, T, Leon, AC, Mayo, DJ, Patrick, DL, Patterson, TL, Rose, A, Stover, E and Wykes, T (2007) Assessment of community functioning in people with schizophrenia and other severe mental illnesses: a white paper based on an NIMH-sponsored workshop. Schizophrenia Bulletin 33, 805–822.Google Scholar
Boot, E, Butcher, NJ, van Amelsvoort, TA, Lang, AE, Marras, C, Pondal, M, Andrade, DM, Fung, WL and Bassett, AS (2015) Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome. American Journal of Medical Genetics A 167A, 639–645.Google Scholar
Bosia, M, Buonocore, M, Bechi, M, Spangaro, M, Pigoni, A, Croci, M, Cocchi, F, Guglielmino, C, Bianchi, L, Smeraldi, E and Cavallaro, R (2017) Cognitive remediation and functional improvement in schizophrenia: is it a matter of size? European Psychiatry 40, 26–32.Google Scholar
Buchanan, RW, Davis, M, Goff, D, Green, MF, Keefe, RS, Leon, AC, Nuechterlein, KH, Laughren, T, Levin, R, Stover, E, Fenton, W and Marder, SR (2005) A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophrenia Bulletin 31, 5–19.Google Scholar
Butcher, NJ, Chow, EW, Costain, G, Karas, D, Ho, A and Bassett, AS (2012) Functional outcomes of adults with 22q11.2 deletion syndrome. Genetics in Medicine 14, 836–843.Google Scholar
Carlsson, R, Nyman, H, Ganse, G and Cullberg, J (2006) Neuropsychological functions predict 1- and 3-year outcome in first-episode psychosis. Acta Psychiatrica Scandinavica 113, 102–111.Google Scholar
Carrion, RE, McLaughlin, D, Goldberg, TE, Auther, AM, Olsen, RH, Olvet, DM, Correll, CU and Cornblatt, BA (2013) Prediction of functional outcome in individuals at clinical high risk for psychosis. JAMA Psychiatry 70, 1133–1142.Google Scholar
Cattell, RB (1978) The Scientific use of Factor Analysis. New York: Plenum.Google Scholar
Cheung, EN, George, SR, Andrade, DM, Chow, EW, Silversides, CK and Bassett, AS (2014) Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome. Genetics in Medicine 16, 40–44.Google Scholar
Chow, EW, Watson, M, Young, DA and Bassett, AS (2006) Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophrenia Research 87, 270–278.Google Scholar
Costa, PS, Santos, NC, Cunha, P, Palha, JA and Sousa, N (2013) The use of Bayesian latent class cluster models to classify patterns of cognitive performance in healthy ageing. PLoS One 8, e71940.Google Scholar
Dominguez, MD, Viechtbauer, W, Simons, CJ, van Os, J and Krabbendam, L (2009) Are psychotic psychopathology and neurocognition orthogonal? A systematic review of their associations. Psychological Bulletin 135, 157–171.Google Scholar
Drew, LJ, Crabtree, GW, Markx, S, Stark, KL, Chaverneff, F, Xu, B, Mukai, J, Fenelon, K, Hsu, PK, Gogos, JA and Karayiorgou, M (2011) The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders. The International Journal of Developmental Neuroscience 29, 259–281.Google Scholar
Everitt, BS (1975) Multivariate analysis: the need for data, and other problems. British Journal of Psychiatry 126, 237–240.Google Scholar
Fett, AK, Viechtbauer, W, Dominguez, MD, Penn, DL, van Os, J and Krabbendam, L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neuroscience & Biobehavioral Reviews 35, 573–588.Google Scholar
Fisher, M, Loewy, R, Hardy, K, Schlosser, D and Vinogradov, S (2013) Cognitive interventions targeting brain plasticity in the prodromal and early phases of schizophrenia. The Annual Review of Clinical Psychology 9, 435–463.Google Scholar
Fung, WL, McEvilly, R, Fong, J, Silversides, C, Chow, E and Bassett, A (2010) Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome. American Journal of Psychiatry 167, 998.Google Scholar
Glenthoj, LB, Hjorthoj, C, Kristensen, TD, Davidson, CA and Nordentoft, M (2017) The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review. NPJ Schizophrenia 3, 20.Google Scholar
Gold, JM (2004) Cognitive deficits as treatment targets in schizophrenia. Schizophrenia Research 72, 21–28.Google Scholar
Gorsuch, RL (1983) Factor Analysis. 2nd edn. Hillsdale, NJ: Erlbaum.Google Scholar
Green, MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry 153, 321–330.Google Scholar
Green, MF, Kern, RS, Braff, DL and Mintz, J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophrenia Bulletin 26, 119–136.Google Scholar
Hair, JFJ, Anderson, RE, Tatham, RL and Black, WC (1995) Multivariate Data Analysis. 4th edn. Saddle River, NJ: Prentice Hall.Google Scholar
Harave, VS, Shivakumar, V, Kalmady, SV, Narayanaswamy, JC, Varambally, S and Venkatasubramanian, G (2017) Neurocognitive impairments in unaffected first-degree relatives of schizophrenia. Indian Journal of Psychological Medicine 39, 250–253.Google Scholar
Heinrichs, RW and Zakzanis, KK (1998) Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426–445.Google Scholar
Hoff, A and Kremen, W (2003) Neuropsychology in schizophrenia: an update. Current Opinion in Psychiatry 16, 149–155.Google Scholar
Holthausen, EA, Wiersma, D, Cahn, W, Kahn, RS, Dingemans, PM, Schene, AH and van den Bosch, RJ (2007) Predictive value of cognition for different domains of outcome in recent-onset schizophrenia. Psychiatry Research 149, 71–80.Google Scholar
Insel, TR (2010) Rethinking schizophrenia. Nature 468, 187–193.Google Scholar
Kline, P (1979) Psychometrics and Psychology. London: Academic Press.Google Scholar
Kurtz, MM and Mueser, KT (2008) A meta-analysis of controlled research on social skills training for schizophrenia. The Journal of Consulting and Clinical Psychology 76, 491–504.Google Scholar
Lattin, JM, Carroll, JD and Green, PE (2003) Analyzing Multivariate Data. Pacific Grove, CA: Brooks/Cole – Thomson Learning.Google Scholar
Limperopoulos, C, Majnemer, A, Shevell, MI, Rosenblatt, B, Rohlicek, C, Tchervenkov, C and Darwish, HZ (2001) Functional limitations in young children with congenital heart defects after cardiac surgery. Pediatrics 108, 1325–1331.Google Scholar
Maeder, J, Schneider, M, Bostelmann, M, Debbane, M, Glaser, B, Menghetti, S, Schaer, M and Eliez, S (2016) Developmental trajectories of executive functions in 22q11.2 deletion syndrome. Journal of Neurodevelopmental Disorders 8, 10.Google Scholar
Mariano, MA, Tang, K, Kurtz, M and Kates, WR (2015) Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention. Schizophrenia Research 166, 283–289.Google Scholar
McDonald-McGinn, DM, Sullivan, KE, Marino, B, Philip, N, Swillen, A, Vorstman, JA, Zackai, EH, Emanuel, BS, Vermeesch, JR, Morrow, BE, Scambler, PJ and Bassett, AS (2015) 22q11.2 deletion syndrome. Nature Reviews Disease Primers 1, 15071.Google Scholar
Preacher, KJ and MacCallum, RC (2002) Exploratory factor analysis in behavior genetics research: factor recovery with small sample sizes. Behavioral Genetics 32, 153–161.Google Scholar
Reichenberg, A and Harvey, PD (2007) Neuropsychological impairments in schizophrenia: integration of performance-based and brain imaging findings. Psychological Bulletin 133, 833–858.Google Scholar
Santos, NC, Costa, PS, Amorim, L, Moreira, PS, Cunha, P, Cotter, J and Sousa, N (2015) Exploring the factor structure of neurocognitive measures in older individuals. PLoS One 10, e0124229.Google Scholar
Sitskoorn, MM, Aleman, A, Ebisch, SJ, Appels, MC and Kahn, RS (2004) Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285–295.Google Scholar
Snitz, BE, Macdonald, AW III and Carter, CS (2006) Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophrenia Bulletin 32, 179–194.Google Scholar
Sommer, IE, Bearden, CE, van Dellen, E, Breetvelt, EJ, Duijff, SN, Maijer, K, van Amelsvoort, T, de Haan, L, Gur, RE, Arango, C, Diaz-Caneja, CM, Vinkers, CH and Vorstman, JA (2016) Early interventions in risk groups for schizophrenia: what are we waiting for? NPJ Schizophrenia 2, 16003.Google Scholar
Sparrow, S, Balla, D and Cichetti, D (1984) Vineland Adaptive Behavior Scales. Circle Pines: American Guidance Service.Google Scholar
St-Laurent, M, McCormick, C, Cohn, M, Misic, B, Giannoylis, I and McAndrews, MP (2014) Using multivariate data reduction to predict postsurgery memory decline in patients with mesial temporal lobe epilepsy. Epilepsy & Behavior 31, 220–227.Google Scholar
Swillen, A and McDonald-McGinn, D (2015) Developmental trajectories in 22q11.2 deletion. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 169, 172–181.Google Scholar
Testa, R, Bennett, P and Ponsford, J (2012) Factor analysis of nineteen executive function tests in a healthy adult population. Archives of Clinical Neuropsychology 27, 213–224.Google Scholar
Van, L, Boot, E and Bassett, AS (2017) Update on the 22q11.2 deletion syndrome and its relevance to schizophrenia. Current Opinion in Psychiatry 30, 191–196.Google Scholar
Van, L, Butcher, NJ, Costain, G, Ogura, L, Chow, EW and Bassett, AS (2016) Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome. Genetics in Medicine 18, 350–355.Google Scholar
van Amelsvoort, T, Henry, J, Morris, R, Owen, M, Linszen, D, Murphy, K and Murphy, D (2004) Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome. Schizophrenia Research 70, 223–232.Google Scholar
Velthorst, E, Zinberg, J, Addington, J, Cadenhead, KS, Cannon, TD, Carrion, RE, Auther, A, Cornblatt, BA, McGlashan, TH, Mathalon, DH, Perkins, DO, Seidman, LJ, Tsuang, MT, Walker, EF, Woods, SW, Reichenberg, A and Bearden, CE (2018) Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis. Development and Psychopathology 30, 39–47.Google Scholar
Vorstman, JA, Breetvelt, EJ, Duijff, SN, Eliez, S, Schneider, M, Jalbrzikowski, M, Armando, M, Vicari, S, Shashi, V, Hooper, SR, Chow, EW, Fung, WL, Butcher, NJ, Young, DA, McDonald-McGinn, DM, Vogels, A, van Amelsvoort, T, Gothelf, D, Weinberger, R, Weizman, A, Klaassen, PW, Koops, S, Kates, WR, Antshel, KM, Simon, TJ, Ousley, OY, Swillen, A, Gur, RE, Bearden, CE, Kahn, RS, Bassett, AS and International Consortium on, B. & Behavior in 22q11.2 Deletion, S. (2015) Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry 72, 377–385.Google Scholar
Wechsler, D (1981) Wechsler Adult Intelligence Scale – Revised. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D (1997) Wechsler Adult Intelligence Scale-III. San Antonio, TX: The Psychological Corporation.Google Scholar
Weinberger, R, Yi, J, Calkins, M, Guri, Y, McDonald-McGinn, DM, Emanuel, BS, Zackai, EH, Ruparel, K, Carmel, M, Michaelovsky, E, Weizman, A, Gur, RC, Gur, RE and Gothelf, D (2016) Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome. European Neuropsychopharmacology 26, 1610–1618.Google Scholar
Winter, JCF, Dodou, D and Wieringa, PA (2009) Exploratory factor analysis with small sample sizes. Multivariate Behavioral Research 44, 147–181.Google Scholar
Wykes, T, Huddy, V, Cellard, C, McGurk, SR and Czobor, P (2011) A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. American Journal of Psychiatry 168, 472–485.Google Scholar
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